Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

ObjectiveTo explore the function of DANCR during the differentiation of human embryonic stem cells （hESC） toward definitive endoderm （DE）. MethodsThe in vitro DE differentiation system was established and its efficiency was verified. The correlation between the expression level of DANCR and DE differentiation process was detected. Using lentivirus system， we stably knocked down DANCR in hESC. The shDANCR hESC line was applied to DE differentiation， using qPCR and Western blot to detect the expression of DE marker genes SOX17 and FOXA2， and that of primitive streak marker genes Brachyury （T）， EOMES， MIXL1 and GSC. Dual luciferase reporter assay and qPCR were used to confirm the interaction between DANCR and the WNT pathway during DE differentiation. ResultsThe in vitro differentiation system mimicked DE differentiation efficiently. And the expression of DANCR was gradually downregulated during differentiation. DANCR was efficiently knocked down in the shDANCR hESC line （P < 0.001）. Compared with those in the control group， the expression levels of primitive markers Brachyury （T）， EOMES， MIXL1 and GSC， as well as DE markers SOX17 and FOXA2， were significantly decreased in shDANCR groups （P < 0.05）. Furthermore， the transcriptional activity of the WNT pathway in shDANCR groups was lower than that in the control group （P < 0.05）. And RNA levels of downstream genes of the WNT pathway， FZD5， FZD8， SFRP1， FRZB and ANKRD6， were significantly decreased in shDANCR groups （P < 0.05）. However， differences in protein levels of the TGFβ pathway effectors SMAD2/3 and p-SMAD2 were statistically insignificant in shDANCR and control groups （P > 0.05）. Forced activation of β-CATENIN rescued DANCR knock down-induced deficiency in DE differentiation. ConclusionsThe expression of DANCR decreases during DE differentiation. DANCR may promote DE differentiation through modulating the activity of the WNT pathway.

Objective To analyze the predictive value of serum levels of procalcitonin(PCT)and cytokines on the prognosis of patients with COVID-19 at admission.Methods From November 2022 to February 2023,patients diagnosed with COVID-19 who were admitted to Beijing Chest Hospital were enrolled.Chemiluminescence was used to detect serum PCT levels,and flow microsphere array was used to detect serum cytokines IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17A,IL-17F,IL-22,TNF-α,TNF-β,IFN-γ level.ICU admission,mechanical ventilation and in-hospital death were defined as poor prognosis.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.Results A total of 176 patients with complete data were included,including 134 in the PCT-normal group and 42 in the PCT-elevated group,with a median age of 71.50 years and 71.59%males.Patients in the PCT elevated-group had significantly higher rates of ICU admission(38.41%vs.13.11%,P<0.05),mechanical ventilation(76.92%vs.24.59%,P<0.001)and in-hospital mortality(38.46%vs.6.56%,P<0.001)were significantly higher than those in the PCT-normal group.Serum levels of cytokines IL-6(7.40 pg/mL vs.4.78 pg/mL,P = 0.033 4)and IL-8(10.97 pg/mL vs.5.92 pg/mL,P<0.001)were significantly higher in patients with poor prognosis than in those with good prognosis.The area under the curve for PCT,IL-6,and IL-8 to predict poor prognosis in COVID-19 patients was 0.687,0.660,and 0.746,respectively;sensitivity was 52.78%,55.17%,and 72.41%,respectively;and specificity was 81.58%,74.19%,and 74.19%,respectively,as calculated from the ROC curve.When PCT,IL-6 and IL-8 jointly predict the prognosis of COVID-19 patients,the area under the curve is 0.764,the sensitivity is 70.00%,and the specificity is 80.00%.Conclusion Serum PCT and cytokines IL-6 and IL-8 could be used as predictive markers for poor prognosis in patients with COVID-19.

The theory of "liver opens at the eyes" was first seen in Yellow Emperor's Internal Canon of Medicine， which is the ancient people's summary of the connection between the liver and the eyes. The theory of "liver opens at the eyes" suggests the characteristic of "co-damage and co-recover of liver and eyes". It has been found in clinical practice that liver diseases and eye diseases often occur together， and "liver and eyes co-recover" is an ideal choice. The key to achieving "liver and eyes co-recover" is to analyze its pharmacological material basis and mechanism. With the development of modern medicine， more and more evidence indicates that the liver and eyes have complex and close relationships in physiological and pathological aspects. In a pathological state， there is a phenomenon of "liver and eyes co-damage"， and after the intervention of traditional Chinese medicine， "liver and eyes co-recover" occurs. "Liver and eyes co-damage and co-recover" can be explained through the "co-material basis and co-action mechanism". On this basis， the research group tentatively proposed that the liver and eyes had "four common characteristics" （4CCs）， namely "co-damage， co-recover， co-material basis， and co-action mechanism" from the theoretical connotation of traditional Chinese medicine， clinical practice， and molecular biology. Additionally， the group also took the intervention of Prunella vulgaris， traditional Chinese medicine， for removing liver fire and improving eyesight on immune liver injury （ILI） and allergic conjunctivitis （AC） as examples to analyze 4CCs. This project aims to deeply analyze the scientific connotation of the theory of "liver opens at the eyes"， reveal the common characteristics and biological essence of liver and eyes， explore a new research paradigm of "liver and eyes co-recover"， and provide a reference for the study of common problems of multi-organ associated diseases.

Objective:To explore the symptoms in cervical cancer patients during concurrent chemoradiotherapy, identify symptom clusters, and analyze their influencing factors, so as to provide reference for developing precise symptom management strategies.Methods:From March 2022 to March 2023, convenience sampling was used to select 240 cervical cancer patients who underwent concurrent chemoradiotherapy at the Cancer Center of People's Hospital of Guangxi Zhuang Autonomous Region as the research subject. Patients were surveyed using a General Information Questionnaire and the Chinese version of the M.D. Anderson Symptom Inventory (MDASI-C). Symptom clusters were extracted through exploratory factor analysis, and multiple linear regression was used to explore the influencing factors of the severity of symptom clusters.Results:A total of 240 questionnaires were distributed, and 234 valid questionnaires were collected, with an effective recovery rate of 97.50% (234/240). The 5 symptoms with a high incidence in 234 patients with cervical cancer undergoing concurrent chemoradiotherapy were fatigue, restless sleep, nausea, decreased appetite, and vomiting. The 4 symptom clusters identified by exploratory factor analysis were fatigue related symptom cluster, gastrointestinal related symptom cluster, emotional related symptom cluster, and somatic related symptom cluster. Age, educational level, tumor staging, complications, medical insurance type, and pathological type were the influencing factors for the occurrence of symptom clusters ( P<0.05) . Conclusions:Cervical cancer patients experience multiple symptoms during concurrent chemoradiotherapy, which are interrelated and mutually influencing, often in the form of symptom clusters, with fatigue related symptom clusters being severe. Medical and nursing staff should focus on the core symptoms that play a leading role, develop targeted symptom cluster intervention plans based on the core symptoms of fatigue, improve symptom management efficiency and patient quality of life.

Objective:To evaluate the relationship between regional coronary flow reserve (CFR) obtained from cadmium-zinc-telluride SPECT(CZT SPECT) myocardial functional perfusion imaging (MFPI) and invasive fractional flow reserve (FFR) measured during coronary angiography (CAG) and its clinical value in guiding coronary interventions.Methods:Forty-two patients (30 males, 12 females, age (63.3±9.8) years) who completed CZT SPECT MFPI in the First Affiliated Hospital of Nanjing Medical University from June 2022 to September 2022 and underwent CAG within 3 months were included retrospectively. The concordance of CFR and FFR for diagnosing myocardial ischemia (CFR<2.0 and FFR<0.8) was calculated at the vascular level. The diagnostic efficacy of coronary stenosis≥70% for decreased myocardial blood flow (CFR<2.0) was calculated. Kappa test was used to analyze the data. Results:A total of 126 major coronary arteries were identified in 42 patients, of which 30(23.8%) had a CFR<2.0 by CZT SPECT and 33(26.2%) had stenosis≥70% in CAG. A total of 32 coronary vessels were performed with MFPI CFR and FFR measurements, of which 6 were both decreased and 21 were both normal, so the concordance rate was 84.4%(27/32)( Kappa=0.612, P<0.001). Among 33 coronary vessels with stenosis≥70%, 13 were with CFR≥2.0. Among 30 coronary vessels with CFR<2.0, 10 were with stenosis<70%. When using stenosis≥70% to diagnose CFR decreasing, the sensitivity was 66.7%(20/30), specificity was 86.5%(83/96), positive predictive value was 60.6%(20/33), negative predictive value was 89.2%(83/93), and accuracy was 81.7%(103/126). Conclusions:The concordance between CFR and FFR for the diagnosis of myocardial ischemia is good. Nearly 1/3 of the coronary arteries with decreased CFR have stenosis<70%, whereas nearly 40% of the coronary arteries with stenosis≥70% are not result in myocardial ischemia. Regional CFR determined by CZT SPECT may have potentially significant clinical value in the diagnosis of coronary artery disease and decision-making of coronary intervention.

【Objective】 To investigate the detection of pathogenic microorganisms in umbilical cord blood and maternal blood from 2012 to 2021, so as to improve the collection of umbilical cord blood and guarantee the safety of umbilical cord blood hematopoietic stem cells (HSC) . 【Methods】 Detection results of pathogenic microorganisms of umbilical cord blood and maternal blood among 64 077 cases from Tianjin Cord Blood Bank from 2012 to 2021 were retrospectively analyzed. 【Results】 A total of, 2 072 cases (3.23%) were detected positive, among which, 184 cases (0.29%) were positive for aerobic bacteria culture, 1 504 cases (2.34%) were positive for anaerobic bacteria culture, and 384 cases (0.60%) were positive for both aerobic and anaerobic bacteria culture. From 2012 to 2021,the overall positive rate showed a downward trend, with a difference in the positive rate between each year (P<0.05). The positive rate of anaerobic bacteria was higher than that of aerobic bacteria and that of anaerobic and aerobic bacteria (P<0.05). After Gram staining, the microscopic detection rate of bacterial positive samples was highest in G^- bacilli, followed by G⁺ bacilli, G⁺ cocci, G^- cocci and others. Among the 64 077 cases, 169 cases (0.26%) showed reactivity in cord blood tests and 1 231 cases (1.92%) showed reactivity in maternal blood tests. Umbilical cord blood and maternal blood HIV-Ag/Ab tests showed reactivity after initial screening. After confirmation by Western blotting, there was 1 case of uncertain maternal blood, while the rest were negative. The reactive rates of anti-TP (0.12%) and anti- HCV (0.11%) in umbilical cord blood were higher than those of HBsAg (0.03%) and CMV-IgM (1/64 077).There was a difference in the reactive rate of anti-TP detection in umbilical cord blood between different years (P<0.05),while there was no statistically significant difference in that of HBsAg, anti-HCV and CMV-IgM (P> 0.05).The reactive rate of HBsAg in maternal blood (1.38%) was higher than that of CMV-IgM(0.29%) , anti-TP(0.13%) and anti-HCV (0.12%) . There were differences in the reactive rates of HBsAg, anti-HCV ,and anti-TP in maternal blood among different years (P<0.05),and that of HBsAg showed a decreasing trend, while the reactive rate of CMV-IgM was not statistically significant (P>0.05). The reactive rates of HBsAg and CMV-IgM detected in maternal blood were significantly higher than those in umbilical cord blood (P<0.05) . The reactive rates of anti-HCV and anti-TP in maternal blood were consistent with those in umbilical cord blood (P>0.05). 【Conclusion】 The reactive rates of anti-HIV and CMV-IgM in cord blood, and that of anti-HIV in maternal blood are low, but those of anti-TP and anti-HCV in cord blood are relatively high. The reactive rate of HBsAg is high in maternal blood,but with a downward trend,but low in umbilical cord blood due to maternal-infantile transmission blocking. The detection of transfusion transmitted pathogens and bacteria plays a critical role on the safety of umbilical cord blood HSCs. Effective detection of transfusion transmitted pathogens and culture of bacteria are the key to ensure the quality of umbilical cord blood, which can improve the safety of umbilical cord blood HSCs transplantation.

Objectives:To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients.Results:1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion:Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.

Objective:To investigate the iodine nutritional status of children in Qingdao City and the effects of prevention and treatment measures on iodine deficiency disorders (IDD), and to provide a scientific basis for guiding residents to scientifically supplement iodine, taking timely targeted prevention and control measures, and scientifically adjusting intervention strategies.Methods:According to "National Iodine Deficiency Disorders Surveillance Program (2016 edition)" and "Iodine Deficiency Disorders Surveillance Program of Shandong Province", from 2018 to 2020, using the cluster sampling method, children aged 8-10 years in Qingdao City were chosen to test their household salt iodine content and random urinary iodine content, and to examine their thyroid volume by B-ultrasonography, and the correlation between thyroid volume and physical development indexes was analyzed.Results:From 2018 to 2020, a total of 6 057 children were monitored, including 3 068 boys and 2 989 girls. The median of salt iodine and iodized salt iodine of children was 23.50 and 24.10 mg/kg. The qualified rate of iodized salt was 89.95% (4 832/5 372), the coverage rate of iodized salt was 88.69% (5 372/6 057), and the consumption rate of qualified iodized salt was 79.78% (4 832/6 057). There were significant differences in the qualified rate of iodized salt, the coverage rate of iodized salt and the consumption rate of qualified iodized salt between different years (χ 2 = 135.26, 314.71, 342.87, P < 0.001). A total of 6 057 urine samples were collected from children, and the median of urinary iodine was 193.92 μg/L, of which 16.2% (979/6 057) were < 100 μg/L, and 22.5% (1 361/6 057) were ≥300 μg/L. There were statistically significant differences in the medians of urinary iodine between different years, gender and whether eating iodized salt ( H/Z = 37.25,-3.89,-5.69, P < 0.001), the median of urinary iodine in boys was higher than that of girls, and the median of urinary iodine in eating iodized salt group was higher than that of eating non-iodized salt group. There was no significant difference in the median of urinary iodine between different age ( H = 4.33, P = 0.119). The rate of goiter in children was 3.45% (71/2 057), and the difference between different years was statistically significant (χ 2 = 42.68, P < 0.001). The incidence of goiter in 2020 [7.31% (45/616)] was significantly higher than that in 2018 and 2019 [2.81% (18/641), 1.00% (8/800), P < 0.001]. Thyroid volume of children was positively correlated with height and weight ( r = 0.20, 0.22, P < 0.001). Conclusions:The iodine nutritional level of children aged 8-10 years in Qingdao City is appropriate. However, the incidence of goiter in children in some years is relatively high. The qualified rate of iodized salt, the coverage rate of iodized salt and the consumption rate of qualified iodized salt are all lower than the national standard for elimination of IDD, which should be paid attention to.

Objective:To evaluate the effect of prevention and control measures to drinking-water-borne endemic fluorosis in Qingdao, and to provide scientific basis for formulating prevention and control strategies.Methods:From 2019 to 2021, a full coverage surveillance was carried out in 1 146 villages in 7 drinking-water-borne endemic fluorosis areas in Qingdao, including the operation status of the water improvement and fluoride reduction project, the water fluoride content in the villages, and the prevalence of dental fluorosis among children aged 8-12 years.Results:From 2019 to 2021, all the 1 146 affected villages in Qingdao had improved their water supply, and the rates of water fluoride exceeding the standard were 7.16% (82/1 146), 1.40% (16/1 146) and 3.84% (44/1 146), respectively, and the differences between years were statistically significant (χ 2 = 48.36, P < 0.001). The detection rates of dental fluorosis in children aged 8-12 years were 3.11% (803/25 856), 2.68% (629/23 460) and 3.00% (655/21 846), respectively, and the differences between years were statistically significant (χ 2 = 8.26, P = 0.016). The detection rate of dental fluorosis among children in villages with qualified water fluoride (2.85%, 1 986/69 565) was lower than that in villages with excessive water fluoride (6.32%, 101/1 597), with a statistically significant difference (χ 2 = 67.74, P < 0.001). Conclusions:From 2019 to 2021, the effect of prevention and control measures to drinking-water-borne endemic fluorosis in Qingdao is significant and the detection rate of dental fluorosis in children is low, the detection rate of dental fluorosis in villages with qualified water fluoride is significantly lower than that in villages with excessive water fluoride. In the future, we should continue to strengthen water fluoride monitoring and engineering maintenance to ensure that the water fluoride content continues to be qualified and effectively reduce the harm of fluorosis.